29586-76-3

Upstream product

• 1008-76-0 4,5-dihydro-5-phenyl-2(3H)-furanone 
• 2051-95-8 succinylbenzene 

Downstream Products

• 111138-02-4 (-)-(S)-5-phenyl-4,5-dihydrofuran-2(3H)-one 

Relevant academic research and scientific papers

Selective reductions. 59. Effective intramolecular asymmetric reductions of α-, β-, and γ-keto acids with diisopinocampheylborane and intermolecular asymmetric reductions of the corresponding esters with B-chlorodiisopinocampheylborane

A comparison of the stereochemistry of the products obtained from the intramolecular asymmetric reduction of a series of keto acids with (-)-diisopinocampheylborane and intermolecular asymmetric reduction of the corresponding series of keto esters with (-)-B-chlorodiisopinocampheylborane ((-)-DIP-Chloride) has been made. The stereochemistry of the hydroxy acids from the reduction of keto acids is dependent only on the enantiomer of the reagent used. The stereochemistry of the products from the reduction of keto esters is also consistent, except those of aliphatic α-keto esters. α-, β-, and γ-keto acids provide the corresponding hydroxy acids in 77-98% ee, and the α- and γ-keto esters afford the hydroxy esters in 82-≥99% ee. β-Keto esters do not undergo reduction. Although the reduction of δ-keto acids does not proceed under the same reaction conditions, the reduction of δ-keto esters is facile. All of the products from the reduction of γ-keto acids and esters and δ-keto esters were converted to the corresponding lactones. This study revealed that DIP-Chloride is an efficient reagent for the reduction of α-keto esters at low temperatures.

Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases

Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ～100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.

Efficient intramolecular asymmetric reductions of α-, β-, and γ-keto acids with diisopinocampheylborane1

(equation presented) α-, β-, and γ-Keto acids are reduced with diisopinocampheylborane at room temperature to the corresponding hydroxy acids with predictable stereochemistry in very high ee. The γ-hydroxy acids produced were conveniently cyclized to the corresponding lactones. This provides a simple synthesis of 4-hexanolide, a component of the pheromone secreted by the female dermestid beetle Trogoderma glabrum.

The Esterase Catalysed Resolution of Lactones and Spirodilactone

The pig liver esterase catalysed hydrolysis of spirodilactone and γ-phenyl-γ-butyrolactone gives optically active products (>90percent e.e., after 50percent reaction).However, the similarly substituted acyclic ester analogues of the lactone do not exhibit enantioselectivity suggesting that the acylation step shows the selectivity.Racemic spirodilactone can be converted, in principle, entirely into one of its enantiomers.